Strategies to improve the immunosuppressive properties of human mesenchymal stem cells

Lee, Myoung Woo; Ryu, Somi; Kim, Dae Seong; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

doi:10.1186/s13287-015-0178-y

Cited by 46 publications

(34 citation statements)

References 135 publications

(157 reference statements)

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“…There are evidences suggesting that MSCs produce immune modulatory and regenerative factors in response to inflammatory stimuli, in fact, it may be possible to enhance or suppress certain functions of MSCs by controlling their culture conditions, in particular, priming of MSCs with IFNγ and TNFα successfully improved their immunomodulatory functions 27 . Specifically, treatment with IFNγ up-regulated several genes involved in immunomodulation, such as HLA-DRA, CD274B7, IDO, VCAM1, ICAM2, and chemokines such as CCL8, CXCL9 and CXCL10 28 . In addition, an in vitro model showed that, after priming with TNFα plus IFNγ, MSCs were less potent at increasing cytokine production by activated PBMCs and more effective at inhibiting T-cell proliferation 29 .…”

Section: Discussionmentioning

confidence: 99%

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

Domenis

Cifù

Quaglia

et al. 2018

Sci Rep

196

165

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The predominant mechanism by which adipose mesenchymal stem cells (AMSCs) participate to tissue repair is through a paracrine activity and their communication with the inflammatory microenvironment is essential part of this process. This hypothesis has been strengthened by the recent discovery that stem cells release not only soluble factors but also extracellular vesicles, which elicit similar biological activity to the stem cells themselves. We demonstrated that the treatment with inflammatory cytokines increases the immunosuppressive and anti-inflammatory potential of AMSCs-derived exosomes, which acquire the ability to shift macrophages from M1 to M2 phenotype by shuttling miRNA regulating macrophages polarization. This suggests that the immunomodulatory properties of AMSCs-derived exosomes may be not constitutive, but are instead induced by the inflammatory microenvironment.

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Section: Discussionmentioning

confidence: 99%

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

Domenis

Cifù

Quaglia

et al. 2018

Sci Rep

196

165

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“…Many studies referring to MSC tracing have demonstrated that intravenously engrafted MSCs are mostly intercepted by microvessels of the lung, heart, liver, kidney, etc., as well as homing to inflammatory and injured areas [11–14]. Importantly, MSCs have been shown to have regenerative, anti-inflammatory, and immunomodulatory capabilities [15–17]. Many experiments and early clinical trials have indicated that MSCs can block the rejection or even induce immune tolerance following transplantation [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

et al. 2016

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BackgroundWe determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.MethodsWe performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls. The animals were sacrificed after 1, 5, 7, or 10 days. At each time point, we measured small bowel histology and apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity, cytokine concentrations in serum and intestinal graft, and levels of regulatory T (Treg) cells.ResultsThe saline-treated control group showed aggravated acute cellular rejection over time, with mucosal destruction, increased apoptosis, NK cell activation, and upregulation of proinflammatory and immune-related mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited attenuated acute cellular rejection at an early stage, but the effects receded 7 days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group demonstrated significantly attenuated acute cellular rejection, reduced apoptosis and NK cell activity, and suppressed concentrations of inflammation and immune-related cytokines, and upregulated expression of anti-inflammatory cytokine mediators and increased Treg cell levels.ConclusionOur data suggest that Ad/HO-1-transduced BMMSCs have a reinforced effect on reducing acute rejection and protecting the outcome of SBTx in rats.

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“…Since ECM/SVF-gel contains concentrated ECM components, it may likely serve as a stimulus for the robust inflammation response during the early stages of wound healing. In cytotherapeutic strategies, MSCs have recently been shown to have various immunomodulatory effects on host immune cells in both wound healing and transplant biology [ 45 – 48 ]. To release immunosuppressive factors, MSCs can downregulate the inflammatory response and move the wound past the state of persistent inflammation, conferring the cells with immune privilege and making them an attractive cell type for the treatment of chronic wounds [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

Sun

Zhou

et al. 2017

BioMed Research International

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Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and monocyte chemotactic protein-1 (MCP-1) in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation) assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.

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Strategies to improve the immunosuppressive properties of human mesenchymal stem cells

Cited by 46 publications

References 135 publications

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

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